Ontology highlight
ABSTRACT: Patients and methods
3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapy?+/- intravenous ZOL 4?mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects.Results
With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HRDFS ?=?0.94, 95%CI?=?0.84-1.06, p?=?0.340; HRIDFS ?=?0.91, 95%CI?=?0.82-1.02, p?=?0.116). However, outcomes remain improved with ZOL in postmenopausal women (HRDFS ?=?0.82, 95%CI?=?0.67-1.00; HRIDFS ?=?0.78, 95%CI?=?0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HRIDFS ?=?0.75, 95%CI?=?0.58-0.97) and OS HROS ?=?0.69, 95%CI?=?0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISH?+?tumors. Bone metastases as a first DFS recurrence (BDFS) were reduced with ZOL (HRB-DFS ?=?0.76, 95%CI?=?0.63-0.92, p?=?0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred.Conclusions
Disease benefits with adjuvant ZOL in postmenopausal early breast cancer persist at 10 years of follow-up. The biomarker MAF identified a patient subgroup that derived benefit from ZOL irrespective of menopausal status.
SUBMITTER: Coleman RE
PROVIDER: S-EPMC6303395 | BioStudies | 2018-01-01
REPOSITORIES: biostudies